828P - Expected versus observed response to platinum-based chemotherapy after poly (ADP-ribose) polymerase inhibitor treatment for relapsed ovarian cancer

Background

Poly(ADP-ribose) polymerase inhibitors (PARPi) have become standard of care after response to platinum-based chemotherapy (CTX) for relapsed ovarian cancer (OC). Recently, PARPi have been approved as maintenance after first-line treatment as well. Response to platinum is the key predictor for response to PARPi treatment. Sensitivity and resistance to platinum and PARPi treatment partially overlaps. It remains unclear how prior progression on PARPi treatment might influence response to subsequent platinum-based CTX.

Methods

Patients undergoing platinum-based CTX for 2^nd relapse of epithelial OC treated between 2011 and 2020 at the department of gynecologic oncology at Kliniken Essen-Mitte were included in this retrospective study. All patients provided written consent for retrospective analyses. Stratification parameter were defined as follows: Response to 2^nd line CTX, PARPi maintenance, cytoreductive surgery for relapsed OC, BRCA status, PFS and treatment-free interval for platinum (TFIp) after 2^nd line CTX. Primary outcome parameter was response to 3^rd-line platinum-based CTX in patient with and without prior PARPi treatment.

Results

After response to 2^nd-line CTX, 57 patients received no PARPi (control) and 35 patients received a PARPi (n=16 olaparib, n=19 niraparib) as maintenance therapy. Baseline characteristics were well balanced between treatment groups. After PARPi maintenance 40% (14/35) of patients progressed on subsequent platinum-based CTX vs 9% (5/57) in the control group. Response to 3^rd line platinum-based CTX, evaluated as complete response, partial response, stable disease and progressive disease, was significantly altered by prior PARPi maintenance therapy (χ² 14.19 – df 3 – p=0.003).

Conclusions

Response to platinum-based 3^rd line chemotherapy is lower than expected in patients treated with PARPi maintenance after response to 2^nd line platinum-based chemotherapy, compared to patients who achieved a similar PFS and TFIp who did not receive a PARPi. Our data provide clinical evidence for altered sensitivity towards platinum-based CTX after prior PARPi treatment.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

T. Baert: Advisory/Consultancy: Tesaro; Research grant/Funding (institution): Amgen; Travel/Accommodation/Expenses: Amgen; Travel/Accommodation/Expenses: MSD; Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: Tesaro. B. Ataseven: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Honoraria (self): AstraZeneca; Honoraria (self): Clovis; Honoraria (self): Celgene; Advisory/Consultancy, Travel/Accommodation/Expenses: GSK/Tesaro; Advisory/Consultancy: Amgen; Travel/Accommodation/Expenses: PharmaMar. M. Bommert: Travel/Accommodation/Expenses: prIME Oncology. N. Concin: Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Seattle Genetics; Advisory/Consultancy: Mersana; Travel/Accommodation/Expenses: Amgen; Travel/Accommodation/Expenses: Genmab; Travel/Accommodation/Expenses: Roche; Honoraria (self), Travel/Accommodation/Expenses: Medscape. S. Schneider: Honoraria (self): AstraZeneca; Honoraria (self): Roche; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: GSK/Tesaro; Advisory/Consultancy: Clovis. P. Harter: Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self), Research grant/Funding (institution): Roche; Honoraria (self): Sotio; Honoraria (self), Research grant/Funding (institution): Tesaro; Honoraria (self): Stryker; Honoraria (self): Zai Lab; Honoraria (self): MSD; Honoraria (self): Clovis; Honoraria (self): Immunogen; Research grant/Funding (institution): GSK; Research grant/Funding (institution): Boehringer Ingelheim; Research grant/Funding (institution): Medac; Research grant/Funding (institution): Genmab. A. du Bois: Honoraria (self), Research grant/Funding (institution): Roche; Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self), Research grant/Funding (institution): Tesaro; Honoraria (self), Research grant/Funding (institution): Clovis; Honoraria (self), Research grant/Funding (institution): Pfizer; Honoraria (self), Research grant/Funding (institution): Biocad; Honoraria (self), Research grant/Funding (institution): Genmab/Seattle Genetics; Honoraria (self), Research grant/Funding (institution): MSD. F. Heitz: Honoraria (self): Roche; Honoraria (self): AstraZeneca; Honoraria (self): Clovis; Honoraria (self): GSK/Tesaro; Honoraria (self): Molecular Health; Travel/Accommodation/Expenses: PharmaMar; Travel/Accommodation/Expenses: NewOncology. All other authors have declared no conflicts of interest.